1. Field of the Invention
This invention relates to computer-aided graphical representation and design of three-dimensional models of proteins or polynucleotides. The models evolve from computer graphical representations and provide a geometrically and chemically concise and detailed view of binding sites. The models provide sufficient detail to support binding specificity analysis of active sites involved in ligand binding.
2. Description of the Prior Art
Understanding protein structure is critical for developing a complete understanding of protein function. The development of crucial therapeutic agents is enhanced by a complete understanding of protein structure. Several proteins have binding regions for binding ligands and small molecules such as drugs and nucleotides. Among these proteins are receptors such as those involved in endocrine function, immune function, drug transport, and gene regulation. It is also beneficial to understand the ligand binding regions of polynucleotides.
Among the crucial regulatory elements of the mammalian immune system is a network of molecules encoded in the major histocompatibility gene complex (MHC), including the class I and II MHC products. Class I molecules are found on the surface of virtually every cell type, playing a central role in regulating the levels of cytotoxic and other CD8 T cells directed against infection. The closely related class II products are confined to immune cells and regulate the activity of T helper and other CD4 cells. Under normal conditions, class I and II molecules both migrate from the cell surface to its interior, where they bind to proteolytically digested protein fragments having approximately 9 and 13 to 17 amino acids for class I and II molecules, respectively. The complexes then cycle to the cell surface where, if the peptide is from a foreign protein, they are recognized by T cells of the appropriate type. Thus the binding site of the MHC molecules and the structure of the bound segment are of extraordinary interest and importance in understanding the immune system and in designing agents for regulating immune function. The binding sites in other proteins or peptides are also important, and agents for regulating endocrine or gene regulation would benefit from a more complete understanding of protein or peptide structure about the binding regions of those proteins or peptides.
Previous methods for producing molecular models of proteins or polynucleotides have several shortcomings. The classical `ball and stick` method for creating molecular models is most suited to small molecules. Creation of ball and stick models of large molecular weight molecules is time consuming and cumbersome. The ball and stick models of large molecules do not reveal fine structural detail of binding sites such as supplied by the model approach disclosed and claimed in the present invention. Space filling models may likewise be used, but suffer from the same limitations as the ball and stick models.
Stereolithography is more suited to modelling larger molecules, but creation of stereolithographic models is time-consuming and expensive. The stereolithographic models do not depict atom placement, and do not provide a clear resolution of critical binding sites.
These and other disadvantages of the prior art are overcome by the present invention, and a method for generating models of proteins or polynucleotides is provided.